TEM stereometric analyses of glomeruli in aging OVE26 transgenic diabetic mice

Abstract

Glomerular lesions in diabetic nephropathy (DN) have been studied in numerous murine diabetic models, but the critical feature of aging is often absent. Since DN lesions may just begin to develop at about five months of age, we utilized the long‐lived OVE26 transgenic diabetic model for stereometric analyses of DN glomerulopathic aging. Albuminuria was determined by ELISA and TEM stereometry was utilized exclusively to demonstrate morphometric alterations in the glomerular filtration barrier (GFB) in OVE26 mice at 60, 150 and 450 days of age. Relative to age‐matched controls, albuminuria in diabetic mice is significant at 60 days and profound at 120 days. At 150 days, glomerular volume, mesangial, endothelial, and total cell number are significantly increased, while podocyte, endothelial, and total cell density are significantly decreased. Dystrophic changes in the GFB include podocyte effacement, glomerular basement membrane thickening, and increased non‐fenestrated areas of glomerular capillary endothelium. At 450 days most stereometric alterations are exacerbated. Our data indicate that in OVE26 mice, intense albuminuria precedes morphological lesions and could be due to early‐onset hyperglycemia. Most morphological changes occur relatively late in life and appear unrelated to early renal decompensation. It is possible that they may result from prolonged hyperglycemia‐induced oxidative stress.Grant Funding Source: Supported in part by grants R01DK072032, COBRE P20 RR024489, Juvenile Diabetes Research Foundation Grant 1‐200‐88 and the North Dakota Lions Foundation